Development of Methods of Usher Syndrome Gene Therapy (funded January 2007)

Grant SummaryUsher syndrome is the commonest inherited cause of combined blindness and deafness. The progressive vision loss is currently untreatable, although some hearing may be restored with cochlear implants. Several gene mutations have been identified as causes of the disease, including mutations in the usherin, harmonin and myosin VIIa genes. Gene therapy is a promising experimental treatment that has the potential to prevent the loss of hearing and sight in this devastating condition, but it needs to be developed and tested before it can be attempted in human patients.

The purpose of this application is to develop safe and effective gene therapy methods for Usher syndrome. The long-term goal of this project is to facilitate human clinical trials of this therapy. In this proposal, we have brought together a team of clinical and basic science researchers to accomplish the following goals:

(1) To design and produce a delivery system, using a harmless virus, to deliver the normal usherin, harmonin and myosin VIIa genes to the eye and the inner ear.

(2) To determine the best surgical techniques for safe and efficient delivery of this gene therapy vector to the eye and inner ear. These studies will use a nonhuman primate, the rhesus monkey, because the structure of its eyes and ears are most similar to humans, and different in critical ways from other animals such as rodents.

(3) To test the safety of this gene therapy in monkeys by examining them for any possible side effects of the treatment.

There are no animal models that have Usher syndrome, and therefore it is not possible to test the ability of gene therapy to treat or prevent the disease. However, these studies will be able to test the safety of this treatment in healthy animals. Given the very serious nature of the disease and the potential benefit, clear evidence of safety would make it ethically acceptable to conduct a clinical study in human patients.
Through this project, we aim to provide the foundation for use of gene therapy for Usher syndrome.
We plan that this project will lead to the next steps required to initiate a gene therapy clinical trial: manufacture of a safe vector suitable for a human patients, and, based on demonstration of the treatment’s safety, submission of the necessary regulatory documents to the FDA and other federal agencies. With the experience and information derived from the proposed project, our team at the Casey Eye Institute can then build on its extensive patient base and experience with human clinical trials to bring this new therapy to patients with Usher Syndrome.